This invention relates to medical devices, and more particularly, the invention relates to methods of manufacturing various medical devices utilizing the processes of high speed injection molding and semi-solid (slurry-based) die casting applied to biocompatible metals and metal alloys that may have a high melting point temperature. These devices may be made porous to allow such devices to act as a functional drug delivery vehicle.
Several interventional treatment modalities are presently used for heart disease, including balloon and laser angioplasty, atherectomy, and bypass surgery. In typical coronary balloon angioplasty procedures, a guiding catheter having a distal tip is percutaneously introduced through the femoral artery into the cardiovascular system of a patient using a conventional Seldinger technique and advanced within the cardiovascular system until the distal tip of the guiding catheter is seated at the ostium of the coronary arteries. A guide wire is positioned within an inner lumen of a dilatation catheter and then both are advanced through the guiding catheter to the distal end thereof.
The guide wire is first advanced out of the distal end of the guiding catheter into the patient""s coronary vasculature until the distal end of the guide wire crosses a lesion to be dilated, then the dilatation catheter having an inflatable balloon on the distal portion thereof is advanced into the patient""s coronary anatomy over the previously introduced guide wire until the balloon of the dilatation catheter is properly positioned across the lesion.
Once in position across the lesion, the balloon is inflated to compress the plaque of the lesion against the inside of the artery wall and to otherwise expand the inner lumen of the artery. The balloon is then deflated so that blood flow can be resumed through the dilated artery and the dilatation catheter can be removed therefrom.
One problem that can occur during balloon angioplasty procedures is the formation of intimal flaps which can collapse and occlude the artery when the balloon is deflated at the end of the angioplasty procedure. Another problem characteristic of balloon angioplasty procedures is the large number of patients who are subject to restenosis in the treated artery. In the case of restenosis, the treated artery may again be subjected to balloon angioplasty or to other treatments such as by-pass surgery, if additional balloon angioplasty procedures are not warranted. However, in the event of a partial or total occlusion of a coronary artery by the collapse of a dissected arterial lining after the balloon is deflated, the patient may require immediate medical attention, particularly in the coronary arteries.
A focus of recent development work in the treatment of heart disease has been directed to endoprosthetic devices referred to as stents. Stents are generally cylindrically shaped intravascular devices which are placed within an artery to hold it open. The device can be used to reduce the likelihood of restenosis and to maintain the patency of a blood vessel immediately after intravascular treatments. In some circumstances, they can also be used as the primary treatment device where they are expanded to dilate a stenosis and then left in place.
One method and system developed for delivering stents to desired locations within the patient""s body lumen involves crimping a stent about an expandable member, such as a balloon on the distal end of a catheter, advancing the catheter through the patient""s vascular system until the stent is in the desired location within a blood vessel, and then inflating the expandable member on the catheter to expand the stent within the blood vessel. The expandable member is then deflated and the catheter withdrawn, leaving the expanded stent within the blood vessel, holding open the passageway thereof.
Certain metals and metal alloys, including those capable of being used in the manufacture of various medical devices, exhibit dendritic crystal structures at ambient temperatures. These metals and metal alloys are known as being capable of transforming into a thixotropic state upon the application of heating and shearing. The metal or metal alloy forms into a semi-solid slurry while being heated and maintained at a temperature above its solidus temperature (i.e., temperature at which a material forms into a fully solid state) and below its liquidus temperature (i.e., temperature at which a material forms into a fully liquid state). In order to inhibit the formation of dendritic shaped (i.e., tree-like structure) solid particles in the semi-solid slurry, shearing is applied to and maintained in the slurry mixture. Accordingly, this vigorous shearing action results in the formation of primary solids containing discrete, degenerate dendrites or nodules. The remaining unsolidified liquid alloy of the semi-solid slurry surrounds the degenerate dendrites or nodules. It is this combination of materials that results in the semi-solid slurry being in a thixotropic state.
Various apparatuses for processing thixotropic materials, particularly magnesium and aluminum based alloys, are known in the metallurgical art. Such apparatuses typically include a reciprocating extruder having a barrel that is coupled to a mold (see FIGS. 1 and 2). The extruder barrel has inlet and outlet ends at opposite ends of the apparatus. The inlet end is adapted to receive the metallic material from a solid particulate, pelletized or liquid metal feeder. Depending on the condition of the metallic material as it is being received into the extruder barrel, heating elements either increase the temperature of the metallic material or maintain the material at a predetermined temperature in order for the material to be brought into the two phase solidus-liquidus region. The material is formed into an equilibrium state having both solid and liquid phases while in the extruder barrel. A reciprocating screw positioned in the barrel applies a shearing action to the thixotropic or semi-solid slurry material. The thixotropic material is then ready to be transformed into a mold, and thereafter removed once it has solidified into its net shape.
The processes of high speed injection molding and semi-solid (slurry-based) die casting are primarily used in automotive, consumer electronics, and consumer hardware applications. However, there exists a need to apply these processes in the context of medical device applications using certain biocompatible materials in their thixotropic state to form various types of medical devices. The present invention meets these and other needs.
The present invention is directed to methods of manufacturing various types of medical devices utilizing either one of the processes of high speed injection molding or semi-solid (slurry-based) die casting applied to biocompatible metals and metal alloys that may have a high melting point temperature. The processes are further expanded to include the manufacture of porous tubing or devices for use as drug-eluting medical devices, such as stents.
In view of the foregoing, it is apparent that there still exists a need in the metallurgical art for methods of manufacturing various biomedical devices using known and to be developed biocompatible metals and metal alloys in their thixotropic semi-solid state in combination with one of the processes of high speed injection molding and semi-solid (slurry-based) die casting. Accordingly, the processes of high speed injection molding and semi-solid die casting when applied to a select group of biocompatible metals or metal alloys that may have a high melting point temperature provide methods of manufacturing various medical devices and performs, such as stents, stent tubing (e.g., both straight-walled and variable thickness), endovascular grafts, pacemaker leads, anastomosis clips and anastomosis clip tubing, among others. Manufacture of longer lengths of variable thickness tubing would cut down on the amount of waste seen with today""s manufacturing methods of this type of tubing. Further, in consideration of the development of thin radiopaque novel alloys having magnetic resonance imaging (MRI) compatibility, these processes may allow easier manufacture of such new materials. These processes could be expanded to include the manufacture of porous tubing or devices for use as drug-eluting stents.
One aspect of the present invention involves a method of making a medical device. The method includes providing a biocompatible material, and forming a medical device therefrom utilizing a high speed injection molding process. The material can be a biocompatible metal or metal alloy that may have a high melting point temperature. Exemplary of alloy families that may be used as the biocompatible materials include iron-carbon, cobalt based superalloys, cobalt-chromium, tantalum, titanium, nitinol, niobium, niobium-vanadium, niobium-zirconium, niobium-tantalum-zirconium, titanium-tantalum, tantalum-titanium, niobium-tantalum, tantalum-niobium, niobium-titanium, titanium-niobium, tantalum-tungsten, tantalum-tungsten-hafnium, palladium-silver, silver-palladium, and platinum-iridium. An example of a medical device that can be formed in accordance with the high speed injection molding process includes configuring a stent-having a plurality of connected cylindrical rings.
The high speed injection molding process further includes processing the biocompatible material into a semi-solid thixotropic state while being maintained in a thermally controlled chamber. The biocompatible material is processed into the semi-solid thixotropic state by being heated to a temperature above its solidus temperature and below its liquidus temperature. Since the present invention employs the use of certain biocompatible metals or metal alloys that may have a high melting point temperature, the thermally controlled chamber can be modified to have a higher heating capacity by being fabricated from materials that are capable of accommodating these higher temperature requirements. The heating capacity of the thermally controlled chamber is generally dependent on the particular biocompatible material selected. A shearing action is then applied to the semi-solid thixotropic substrate in the thermally controlled chamber. This shearing action can be by mechanical or electromagnetic means. The semi-solid thixotropic material is injection molded at a high speed into a die. The co-injection of dispersoids such as ceramic or oxide into the injection molded thixotropic material can be used to influence the mechanical properties of the substrate. The die can be fabricated from a less heat resistant material that is thermally sprayed or dip coated with a heat resistant material that acts as a thermal barrier and maintains the integrity of the die. Alternatively, the die can be fabricated entirely from heat resisting materials. The injection molded thixotropic material begins to solidify as it cools. After the material sufficiently cools, it can be removed from the die. Appropriate post-processing steps can be applied to the medical device or perform for further completion of the device.
Another aspect of the present invention involves a method of making a porous medical device utilizing the high speed injection molding process. One way to make the device porous is to mix a binder with the biocompatible material while being maintained in the thixotropic state and then inject the mixture into the die. An additional post-processing step can be applied to the medical device for removal of the binder material, e.g., by dissolving in an appropriate solvent or by baking the part to sublimate or vaporize the binder material. After removal of the binder material, the medical device is ready for impregnation with a drug, such as antiplatelets, anticoagulants, antifibrins, antithrombins, and antiproliferatives. For purposes of this invention, the term xe2x80x9cimpregnatexe2x80x9d means to fill throughout or saturate.
In a further aspect of the present invention, a method of making a medical device utilizing the process of semi-solid (slurry-based) die casting is disclosed. The method includes providing a biocompatible material and forming a medical device. Semi-solid die casting is similar to the process of high speed injection molding as set forth above. The biocompatible material is processed into a semi-solid slurry suspension wherein the biocompatible material is heated to a temperature above its solidus temperature and below its liquidus temperature while in a thermally controlled chamber. A shearing force is simultaneously applied to the semi-solid slurry suspension while being maintained in a semi-solid slurry suspension. After being transferred to the die casting device while being maintained in a thermally controlled environment, the semi-solid suspension is die cast into form at a high temperature. The semi-solid suspension solidifies as it cools, after which time the medical device can be removed from the die. The medical device can be made porous for subsequent impregnation with a drug by mixing a binder into the biocompatible material, while being maintained in a semi-solid suspension, and then casting the mixture into the die.
The present invention also involves methods of making tube stock. In particular, the methods include providing a biocompatible material and forming tube stock using one of the processes of high speed injection molding or semi-solid die casting. Exemplary medical devices that can be formed in accordance with the present invention include an intravascular device, a stent, an embolic protection device, an attachment system for an endovascular graft, a guide wire, a wire lead, a catheter, a pacemaker lead end, and an anastomosis device.